Work from this laboratory indicated that the branched chain amino acids, particularly leucine, have a regulatory role in protein turnover in skeletal muscle. The effect of the branched chain amino acids on translation will be studied. Experiments are in progress to demonstrate whether or not regulation of protein turnover by leucine involves only proteins, or is a generalized effect. We reported that the oxidation of branched chain amino acids by muscles is regulated by hormones and metabolites, is accelerated by fasting, diabetes and an increase in the NAD/NADH ratio; alanine release by muscle and the glutamine/ glutamate ration in muscle is altered in diabetes and is increased when NAD/NADH increases. Thus, the redox potential plays a regulatory role in the release of gluconeogenic amino acids from muscles, and exerts a restraining effect on gluconeogenesis and protein catabolism during ketosis. The rate limiting reactions in this phenomenon will be further evaluated. The regulation of the branched chain alpha-keto acid dehydrogenase system, the rate limiting enzyme in branched chain amino acid oxidation by muscles will be studied; the effect of hormones, electrolytes, ATP/ADP, other nucleotides and co-factors will be investigated. Studies concerning the effect of diabetes and insulin on amino acid metabolism by isolated nerves, retinae and aortae will be continued. BIBLIOGRAPHIC REFERENCES: Buse, M.G., Herlong H.F., and Weigand D.A. The effect of diabetes, insulin and the redox potential on leucine metabolism by isolated rat hemidiaphragms. Endocrinology, 98 (May 1976, in press). Buse, M.G., Jursinic S. and Reid S.S. Regulation of branched chain amino acid oxidation in isolated muscles, nerves and aortas of rats. Biochem. J. 148: 363-374, 1975.